αvβ3 Antagonists Based on a Central Thiophene Scaffold

A series of novel, highly potent αvβ3 antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. A number of structural features, such as cyclic versus open guanidine and a variety of lipophilic side chains, carbamates, sulfonamides and β-amino acids were explored with respect to inhibition of αvβ3 mediated cell adhesion and selectivity versus αIIbβ3 binding. In addition, compound 19 was found to be active in the TPTX model of osteoporosis.

A series of novel, highly potent αvβ3 antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. The compound shown was found to be active in the TPTX model of osteoporosis.Figure optionsDownload full-size imageDownload as PowerPoint slide